Chemokines and common variable immunodeficiency; possible contribution of the fractalkine system (CX3CL1/CX3CR1) to chronic inflammation.
Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by defective immunoglobulin production and high frequency of bacterial infections, autoimmunity and manifestations of chronic inflammation. The chemokine Fractalkine (CX3CL1) and its receptor CX3CR1 is suggested to play an important role in the pathogenesis of several inflammatory disorders. We hypothesized that enhanced CX3CL1/CX3CR1 interaction could be involved in the chronic inflammation characterising subgroups of CVID. CVID patients were characterized by raised plasma levels of CX3CLl and enhanced expression of its corresponding receptor CX3CR1 on CD4(+) and CD8(+) T cells, including both CD45RA(+) and CD45RA(-) subsets. CX3CR1 expression was particularly enhanced in patients characterized by chronic inflammation in vivo. The high expression of the receptor in CVID patients was accompanied by enhanced chemotactic, adhesive, and other inflammatory cell responses to stimulation with CX3CL1. Our findings suggest that increased CX3CL1/CX3CR1 interaction could contribute to the inflammatory phenotype seen in subgroups of CVID patients.
Fevang
Børre
B
Research Institute for Internal Medicine, Rikshospitalet, University of Oslo, N-0027 Oslo, Norway. Borre.Fevang@medisin.uio.no
Yndestad
Arne
A
Damås
Jan K
JK
Bjerkeli
Vigdis
V
Ueland
Thor
T
Holm
Are M
AM
Beiske
Klaus
K
Aukrust
Pål
P
Frøland
Stig S
SS
D000328:Adult; D000073883:CX3C Chemokine Receptor 1; D002448:Cell Adhesion / Q000276:immunology; D054428:Chemokine CX3CL1 / Q000097:blood*; D002633:Chemotaxis / Q000276:immunology; D002908:Chronic Disease; D017074:Common Variable Immunodeficiency / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D019707:Receptors, Chemokine / Q000097:blood*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014841:von Willebrand Factor / Q000032:analysis / Q000276:immunology
D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D016207:Cytokines; D019707:Receptors, Chemokine; C029417:Von Willebrand antigen; D014841:von Willebrand Factor